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PHARMACOLOGY

Action at the mu receptor is sufficient to explain the supraspinal analgesic effect of opiates. - F.G. Fang, H.L. Fields and N.M. Lee, J. Pharmacol. Exp. Ther., 238 (1986) 1039-1044.

In this paper the authors addressed the receptor class through which opiates exert their analgesic action when administered intracerebrovent~cul~ly (i.c.v.) in the mouse. Apparent pA, values in naloxone antagonism and rank order potencies were determined for several, relatively selective mu, delta and kappa receptor agonists. Analgesia could be produced by a variety of agonists, including DAGO, a mu agonist and [D-Pen2, D-Pen$nkephahn (DPDPE), a selective delta agonist. Kappa ligands were generally without effect. These data suggested that both mu and delta receptors are involved in supraspinal mediated opiate analgesia. However, apparent pA2 of morphine, DAGO and DPDPE in naloxone antagonism did not differ significantly. It was thus concluded that although mu and delta agonists can produce analgesia by i.c.v. injection, the properties of the mu receptor alone are sufficient to account for those effects.

Role of mu and delta receptors in the supraspinal and spinal analgesic effects of [D-Pen*, D-Pe$‘] enkephalin in the mouse. - F. Porreca, J.S. Heyman, H-1. Mosberg, J.R. Omnaas and J.L. Vaught, J. Pharmacol. Exp. Ther., 241 (1987) 393-400.

This study addressed the receptors that contribute to supraspinal and spinal opiate analgesia in thermal tests of analgesia. Two approaches were taken. First, mice were made tolerant to morphine and the analgesic potencies of mu and delta receptor-specific ligands tested. In another series, the effect of the delta receptor antagonist, ICI 174,864 was used. The authors found that a variety of ligands failed to produce analgesia in the rno~~ne-toler~t mouse, however, the specific delta agonist [D-Pen’, D-Pen’] enkephalin (DPDPE)-produced analgesia when administered intracerebrovent~cularly (i.c.v.). In addition, ICI 174,86 blocked the analgesia produced by i.c.v. DPDPE but not that produced by i.c.v. morphine. In contrast, cross-tolerance was found when DPDPE was administered intrathecally to morphine-tolerant mice. The authors concluded that both mu and delta receptors contribute to the analgesic action of opiates at supraspinal sites. In contrast, the authors’ data support the view that a common site (mu or delta) is involved in the analgesic action of opiates at the level of the spinal cord.

Autoradiographic differentiation of mu, delta aud kappa opioid receptors in the rat forebrain and midbrain. - A. Mansour, H. Khachaturian, M.E. Lewis, H. Akil and S.J. Watson, Neuroscience, 7 (1987) 2445-2464.

The authors have mapped the differential distribution of 3 opioid receptor subtypes using in vitro autoradiography. The selective ligands DAGO, DPDPE, and bremazocine were used to label, respectively, mu, delta and kappa binding sites. Bremazocine binding was performed in the presence of cold mu and delta blockers. Mu binding sites were widespread through the telencephalon and mesencephalon. Signifi- cant delta binding was restricted to the neocortex, paleocortex, caudate/putamen and nucleus accumbens. Kappa sites were densest in the paleocortex, caudate/putamen, nucleus accumbens, hypothalamus, median eminence and amygdala. In the midbrain periaqueductal gray matter (PAG), moderate mu binding was only found dorsolaterally; delta binding was insig~fic~t. Kappa binding was moderate throu~out. This pattern of binding in the PAG conflicts with the conclusions of pharmacological studies (see above).

NEUROSURGERY

Long-term prospective study of hnnbosacral discectomy. - P.J. Lewis, B.K.A. Weir, R.W. Broad and M-G. Grace, J. Neurosurg., 67 (1987) 49-53.

A long-term prospective study of 100 patients undergoing lumbosacral discectomy was carried out in an attempt to delineate the natural history and to assess the significance of certain preoperative factors as

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determinants of long-term outcome. Follow-up using questionnaire and patient examination was carried out at 1 month, 1 year and 5 and 10 years postoperatively~ With a ~nimum follow-up of 5 years, 62$, of the patients had complete relief of back pain and leg pain. 96% were happy that they had undergone the surgery and 93% were able to return to work. 9% reported that their back pain at 5 and 10 years was as severe or worse than preoperatively and 11% reported that their leg pain was as severe or worse than preoperatively. The reoperation rate was 18%. Preoperative factors that were found to be significantly associated with outcome at 1 year postoperatively were not significantly associated with outcome at 5---l 0 years postoperatively. The authors conclude that the results of lumbosacral discectomy appear favorable as evaluated in their study, but comment that preoperative factors useful as predictors of short-term outcome are much less reliable when considering the long-term results.

Inhibition of dorsal horn cell responses by stimulation of the Kolliker fuse nucleus. - C-3. Hodge, Jr., A.V. Apkarian and R.T. Stevens, .I. Neurosurg., 66 (1986) 825-833.

This study examines the effects of stimulation of the Kolliker fuse nucleus (KF) on responses of dorsaf horn neurons to inn~uous and noxious cutaneous stimulation in anesthetised cats. Stimulation of the KF produced potent inhibition of the responses of dorsal horn cells to both types of stimuli but the threshold for responses to noxious stimuli was significantly lower. Depletion of biogenic amines by pretreatment with reserpine resulted in a significant decrease in the KF spinal inhibitory effects, suggesting their dependence on intact noradrenergic stores. The authors feel that the Kolliker-fuse spinal system is an important noradrenergic dependent site for brain-stem modulation of spinal processing of noxious, potentially painful stimuli. They also believe that the KF nucleus is the major source of catecholamine innervation to the spinal cord and believe that the KF nucleus rather than the locus coeruleus and subcoeruleus are the primary nuclei in the so-called parabrachial region of the pons involved in catecholaminergic modulation of spinal nocioception.

Balloon compression rhizolysis in the surgical rn~a~e~~t of trigeminal neuralgia. - C.J. Belber and R.A. Rak, Neurosurgery, 20 (1987) 908-913.

The authors describe their experience in treating trigeminal neuralgia in 25 patients by percutaneous balloon compression rhizolysis of the trigeminal nerve. A no. 4 French Fogarty catheter was guided by fluoroscopy through the foramen ovale into Meckel’s cave and the balloon was inflated tightly for a few minutes with soluble contrast agent to compress the gasserian ganglion rootlets under light endotracheal anesthesia. All patients experienced immediate pain relief with mild numbness in all 3 divisions but with sparing of the cornea1 reflex. There was often transient weakness of the ipsilateral muscles of mastication. 76% of patients followed between 6 months and 7 years had permanent cure of their pain and there were 8 recurrences. The authors believe that the advantages of this procedure include its high rate of efficacy, low rate of dysesthesias, absence of discomfort for the patient during the procedure, short operative time, technical ease of perfor~ng the procedure, minimal morbidity and no risk of loss of cornea1 sensation. The authors believe that microvascular decompression should be the first operation considered for trigeminal neuralgia but that their balloon compression technique is the procedure of choice for the aged and medically infirmed.

Prognostic factors implicated in the microsurgical treatment of trigeminal ueuralgia. - M. Sindou and J. Szapiro, Jr. In: M. Samii (Ed.), Surgery In and Around the Brain Stem and the Third Ventricle, Springer, Heidelberg, 1986, pp. 273-279.

The authors have analyzed the results in 150 patients referred for trigeminal neuralgia and operated upon at the cerebella-pontine angle, i..e, 20% of their total series of 759 patients with tic douloureux (609 of them having been submitted to percutaneous RF thermocoagulation).

In 14 of the above 150 patients, a tumour, an angioma or a giant aneurysm have been found and with its removal a total relief of pain has been obtained.